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ATM facilitates mouse gammaherpesvirus reactivation from myeloid cells during chronic infection. Virology 2015 Sep;483:264-74

Date

05/24/2015

Pubmed ID

26001649

Pubmed Central ID

PMC4516584

DOI

10.1016/j.virol.2015.04.026

Scopus ID

2-s2.0-84929458199   7 Citations

Abstract

Gammaherpesviruses are cancer-associated pathogens that establish life-long infection in most adults. Insufficiency of Ataxia-Telangiectasia mutated (ATM) kinase leads to a poor control of chronic gammaherpesvirus infection via an unknown mechanism that likely involves a suboptimal antiviral response. In contrast to the phenotype in the intact host, ATM facilitates gammaherpesvirus reactivation and replication in vitro. We hypothesized that ATM mediates both pro- and antiviral activities to regulate chronic gammaherpesvirus infection in an immunocompetent host. To test the proposed proviral activity of ATM in vivo, we generated mice with ATM deficiency limited to myeloid cells. Myeloid-specific ATM deficiency attenuated gammaherpesvirus infection during the establishment of viral latency. The results of our study uncover a proviral role of ATM in the context of gammaherpesvirus infection in vivo and support a model where ATM combines pro- and antiviral functions to facilitate both gammaherpesvirus-specific T cell immune response and viral reactivation in vivo.

Author List

Kulinski JM, Darrah EJ, Broniowska KA, Mboko WP, Mounce BC, Malherbe LP, Corbett JA, Gauld SB, Tarakanova VL

Authors

John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of Wisconsin
Vera Tarakanova PhD Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Animals
Ataxia Telangiectasia Mutated Proteins
Chronic Disease
Gammaherpesvirinae
Herpesviridae Infections
Host-Pathogen Interactions
Humans
Mice, Inbred C57BL
Mice, Knockout
Myeloid Cells
Virus Activation
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a